Abstract Background Solid pancreatic serous cystadenoma (SCA) may present as a hypervascular mass and mimic nonfunctioning pancreatic neuroendocrine tumour (NF-pNET), potentially leading to pancreatic resection for benign disease. We synthesized the available evidence on this diagnostic pitfall. Methods A PRISMA 2020–aligned systematic review searched MEDLINE, Embase, and Web of Science (1 January 2000–1 December 2025). We included comparative cohorts of pathology-proven SCA versus NF-pNET reporting CT/MRI discriminative features and case reports/series of pathology-proven SCA preoperatively interpreted as NF-pNET. Comparative cohorts and case reports/series were synthesized separately; no meta-analysis was performed. Results Thirty-five publications were included: four retrospective single-center comparative cohorts (50 SCA and 89 NF-pNET patients) and 31 case reports/series (39 SCA patients). In comparative cohorts, unenhanced CT attenuation was consistently lower in SCA than in NF-pNET (18.5–29.6 vs. 38.8–48.4 HU), with study-specific ROC-derived cutoffs in the low 30-HU range; attenuation ratios performed similarly. Diffusion-weighted MRI showed higher ADC values in SCA, with reported study-specific cutoffs of > 1.36 × 10 − 3 mm 2 /s and > 1.99 × 10 − 3 mm 2 /s. In case reports/series, arterial hyperenhancement occurred in 32/33 (97.0%), 68 Ga-DOTA–peptide uptake in 17/39 (43.6%), and EUS-guided sampling was diagnostic in 9/17 (52.9%). Conclusions NF-pNET–mimicking SCA is an uncommon but clinically consequential benign mimic. In the available retrospective comparative cohorts of resected, pathology-proven lesions, lower unenhanced CT attenuation (and attenuation ratios) and higher DWI–ADC values consistently favored SCA over NF-pNET, whereas arterial hyperenhancement and positive somatostatin receptor imaging uptake were not specific. These findings may support cautious multiparametric assessment in selected hypervascular solid-appearing pancreatic lesions, but should not be applied as definitive diagnostic thresholds without external validation.
Annecchiarico et al. (Sat,) studied this question.